Stem Cells International

Review Article

In Utero Stem Cell Transplantation: Potential Therapeutic Application for Muscle Diseases

Table 1

In utero cell transplantation.
AuthorYearRefHost animalDonor animalCell typeTarget tissueInjection siteInjection stageDiseaseDurationNumber of cellsChimerism
Fleischman et al.1979[29]W/W, Wv/Wv mouseC57Bl/6, DBA/2 mouseFetal liver cell (E13–E15)HematopoiesisIntraplacentalE11No—1 × 105In peripheral blood is more in W/W than in Wv/Wv
Carrier et al.1995[30]BALB/c, C57Bl/6 mouseC57Bl/6 mouseFetal liver cellHematopoiesisIP, intraplacentalE11–13No22–44 weeks5 × 10510–62% (peripheral blood, liver, and spleen)
Archer et al.1997[74]Nod/Scid, C57Bl/6 mouseC57Bl/6-Ly-5.2 mouseBM (lin-depleted)HematopoiesisIPE13.5NoPB analyzed 4 and 26 weeks8 × 105~55% (peripheral blood, spleen, BM)
Kim et al.1999[75]BALB/c mouseDBA/2 mouseBMHematopoiesisIPE14No~8 weeks—Successful skin grafts in 2 of 3 mice
Mackenzie et al.2002[66]mdx C57Bl/10 mouseRosa26 mouseBM, fetal liver cellMultipleIPE14DMD~14 months5 × 106 BM, 1 × 106 fetal liver cellMultiple tissues
Chou et al.2005[76]BALB/c mouseHumanMSC (BM)MultipleIPE13-14No~5 months (postnatal)1 × 105~56% in multiple tissues
Frattini et al.2005[77]Oc+/−C57Bl/6 mouseMouse CD1 CMV-GFPBMHematopoiesisIPE14.5Autosomal recessive osteopetrosis~7 months5 × 106Improved survival
Chan et al.2007[68]MF1 and mdx C57Bl/10 miceHumanMSC (fetal)MuscleIP, yolk sac vein, intramuscularE14–16DMD~18 weeks (postnatal)5 × 103–1 × 106Multiple tissues
Li et al.2007[78]oim/oim mouseMouseMSC (BM)MultipleIP—No——Multiple tissues
Guillot et al.2008[79]oim/oim mouseHumanMSC (fetal)BoneIPE13.5–15Osteogenesis imperfectaE18, 1 week, 2 weeks, 4 weeks, 8 weeks, and 12 weeks—Multiple tissues
Kun-Yi Lin et al.2013[80]MouseMouseAmniotic fluid progenitor cellsMultipleIPE13.5No3, 6, and 9 weeks (postnatal)—Multiple tissues
Ihara et al.2015[81]MPSVII mouseICR/B6 actin-GFP mouseBM (lin-depleted)HematopoiesisIV in vitelline veinE14.5Mucopolysaccharidosis type VII~8 weeks (postnatal)5 × 105Multiple tissues
Cohen et al.2016[52]Mouse (Wsh/Wsh)Mouse, rat, and humanMouse neural crest cell, mESC, riPSC, and hESC/hiPSCMelanocyteIntra-amnioticE8.5NoE10.5–E18.5, postnatal—Skin pigmentation
Boelig et al.2016[31]C57Bl/6TgN mouseC57Bl/6 H-2K actin-GFP mouseBMHematopoiesisIV in vitelline vein, IP, intrahepaticE14No4, 24, 72 hrs, and ~6 months (postnatal)5 × 106 IV, IP, intrahepatic, 2 × 107 IVMultiple tissues
Munoz-Elias et al.2004[82]RatRatMSC (BM)BrainLateral ventricleE15.5NoE17.5, E19.5, and E21.5; 3 days , 1 month, and 2 months (postnatal)—Neuronal tissues
Chen et al.2009[43]RatHumanMSC (placental)MultipleIPE17NoE21, 3 weeks, 12 weeks (postnatal)—~60% in multiple tissues
Li et al.2012[83]Wistar ratWistar ratBM-MSCNeurogenesisLumbosacral spineE16–18Spina bifida apertaE201–6 × 103Neuronal tissues
Munoz-Saez et al.2013[51]Wistar ratWistar rat, FischerFetal hepatocyte (E21)LiverIPE17No~15 days (postnatal)1 × 106Multiple tissues
Li et al.2014[44]RatRatMSC (BM)Spinal cordSpinal columnE16Spina bifida aperta~E20—Spinal cord
Burai et al.2015[84]RatHumanAmniotic cellMultiple—E18No1, 4, 11, and 18 days2 × 105Multiple tissues
Touraine et al.1989[40]HumanHumanFetal liver, thymic epithelial cellHematopoiesisUmbilical vein30 weeksBare lymphocyte syndrome—1.6 × 10710% in lymphocyte
Wengler et al.1996[37]HumanHumanT cell-depleted CD34+ BMHematopoiesisIP21 weeksNo——No GVHD, normal T cell response
Flake et al.1996[36]HumanPaternalBM (CD34+ paternal)HematopoiesisIP16–18.5 weeks—At birth, 3 months, 6 months (postnatal)1.48–2 × 106All T cells
Gil et al.1999[38]HumanHumanBM (paternal CD34+)HematopoiesisIP23 weeks and 23 weeks + 10 daysSCID—1.4 × 107, 6 × 106T cells
Westgren et al.2002[39]HumanHumanFetal liver cell (10 weeks)HematopoiesisIP14 weeksX-linked SCID—7 × 10710% (24 weeks), 50% (33 weeks), all T cells/NK cells are donor origin
Le Blanc et al.2005[46]HumanHumanMSC (fetal liver)BoneUmbilical vein32 weeksOsteogenesis imperfecta—6.5 × 106Normal osteoblast distribution and trabeculae
Götherström et al.2014[85]HumanHumanMSC (7-week, 3-day/10-week fetal liver)LiverIntrahepatic vein31 weeksOsteogenesis imperfecta3–10 years (postnatal)4 × 1077.4%, healed fractures
Harrison et al.1989[35]Rh monkeyRh MonkeyFetal liver cell (days 59–68 opposite sex)HematopoiesisIP60–62 daysNo~2 years1 × 108–1 × 109/kgLymphoid, myeloid, and erythroid, no GVHD
Mychaliska et al.1997[34]MonkeyPaternalBM (T cell depleted)HematopoiesisIP61 daysNo~2 years1 × 108/kg<0.1%, slower progression of rejection after kidney transplants
Shields et al.2003[86]Baboon/cynomolgus monkeyBaboon monkeyBM (parental, T cell-depleted B), T cellHematopoiesisIP0.34–0.38 gestationNo~2 years3 × 109Peripheral blood
Asano et al.2003[87]Cynomolgus monkeyCynomolgus monkeyESCMultipleIP or intrahepaticEnd of 1st trimesterNo1, 3 months (posttransplantation)3.6–4.8 × 106Multiple tissues, small tumor
Crombleholme et al.1990[88]LambSheepBM (whole, T cell depleted)HematopoiesisIP—No——18% (whole), 6% (T cell depleted), No GVHD
Zanjani et al.1994[89]SheepHumanCD45+ cell injected with human fetal HSCHematopoiesisIP50–54 daysNo~68 weeks (postnatal)4.9 × 106Chimerism found in 2 of 6 sheep
Almeida-porada et al.1999, 2000[90, 91]SheepHumanBM + stromal cellHematopoiesisIP55–60 daysNo3, 6, and 9 weeks after transplantation; 3 days, 3 months, and 1–3 years (postnatal)5 × 104–7.5 × 105Peripheral blood
Liechty et al.2000[41]SheepHumanMSC (BM)MultipleIP65 days, 85 daysNo2 weeks, 2 months, 5 months, and 13 months—Multiple tissues
Mackenzie et al.2001[66]SheepHumanMSCMultipleIP65 days, 85 daysNo—2 × 106Multiple tissues in 28 of 29 sheep
Emmert et al.2013[92]SheepHumanMSC (adipose/BM)MultipleIP and intramyocardial70–75 daysNo7–9 days (postnatal)—Multiple tissues
Jeanblanc et al.2014[93]SheepSheep/human (opposite sex)BM (T cell depleted), BM (CD34+), and BM (human CD34+)HematopoiesisIP45 days, 65 daysNo10, 60, and 130 days and ~9 months (posttransplantation)5 × 105 BM, 1.4 × 106 CD34+, and 4 × 104–5 × 105 human CD34+In blood cells at day 65